Morpholines as selective inhibitors of cytochrome P450 2A13

Abstract

A method of inhibiting formation of cancerous metabolites, of inhibiting cytochrome P450 2A13 from forming carcinogen metabolites, and/or inhibiting formation of cancerous lung cells in a subject can include: providing a morpholine compound that selectively interacts with cytochrome P450 2A13 over cytochrome P450 2A6; administering a therapeutically effective amount of the morpholine compound or derivative to the subject. The morpholine compound or derivative can be substantially more selective for interacting with the cytochrome P450 2A13 over the cytochrome P450 2A6. The morpholine compound or derivative can also be substantially non-interactive with other physiological components. The morpholine compound or derivative can include a structure that selectively interacts with cytochrome P450 2A13 over cytochrome P450 2A6, such as Compounds 1-34 of Formulas A-D.

The invention claimed is: 
     
       1. A morpholine compound having the structure: 
       
         
           
           
               
               
           
         
       
       wherein,
 X 3  is O or S; and 
 R 2  is an unsubstituted straight chain or branched C 4 -C 10  alkyl group. 
 
     
     
       2. A pharmaceutical composition comprising
 (a) a morpholine compound having the structure: 
 
       
         
           
           
               
               
           
         
       
       wherein,
 X 3  is O or S; and 
 R 2  is an unsubstituted straight chain or branched C 1 -C 10  alkyl group; and 
 (b) a pharmaceutically acceptable carrier. 
 
     
     
       3. The pharmaceutical composition of  claim 2 , wherein the morpholine compound comprises 4-(2-ethylbenzyl)morpholine, 4-(2-isopropylbenzyl)morpholine or 4-(2-propylbenzyl)morpholine. 
     
     
       4. A method for inhibiting formation of cancerous metabolites in a subject comprising administering to a subject who is a smoker or has been exposed to second hand smoke a therapeutically effective amount of a morpholine compound having the structure 
       
         
           
           
               
               
           
         
       
       so as to inhibit formation of cancerous metabolites of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone by cytochrome P450 2A13, wherein
 X 3  is O or S; and 
 R 2  is an unsubstituted straight chain or branched C 1 -C 3  alkyl group. 
 
     
     
       5. The method of  claim 4 , wherein the morpholine compound is substantially more selective for interacting with the cytochrome P450 2A13 over the cytochrome P450 2A6. 
     
     
       6. The method of  claim 4 , wherein the morpholine compound comprises 4-(2-ethylbenzyl)morpholine, 4-(2-isopropylbenzyl)morpholine or 4-(2-propylbenzyl)morpholine. 
     
     
       7. A method of inhibiting formation of cancerous lung cells in a subject comprising administering to a subject who is a smoker or has been exposed to second hand smoke a therapeutically effective amount of a morpholine compound having the structure 
       
         
           
           
               
               
           
         
       
       so as to inhibit formation of cancerous lung cells resulting from activity of cancerous metabolites of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone, wherein
 X 3  is O or S; and 
 R 2  is an unsubstituted straight chain or branched C 1 -C 3  alkyl group. 
 
     
     
       8. The method of  claim 7 , wherein the morpholine compound is substantially more selective for interacting with the cytochrome P450 2A13 over the cytochrome P450 2A6. 
     
     
       9. The method of  claim 7 , wherein the morpholine compound comprises 4-(2-ethylbenzyl)morpholine, 4-(2-isopropylbenzyl)morpholine or 4-(2-propylbenzyl)morpholine.